Project Abstract The objective of this proposal is to complete clinical validation of the Multiple Biopsy Device (MBD), an endoscopic device that will revolutionize endoscopic practice by improving the efficiency of endoscopic biopsy, eliminating the loss of critical specimens, and improving the safety of endoscopic biopsy for both practitioners and patients. Over 16 million endoscopic procedures will require endoscopic biopsy in the year 2017, and the number of diagnostic endoscopic procedures is expected to grow by 6-8% per year over the next decade. Currently marketed biopsy devices require a separate pass of the device every 1-2 bites. Clinical protocols for endoscopic biopsy require multiple passes to satisfy the total number of specimens needed to achieve diagnostic certainty, adding significant time pressures to already overburdened endoscopists. We have developed a device that will allow the acquisition of an unlimited number of biopsies from one pass of the biopsy device. The MBD operates by mechanically harvesting a mucosal specimen taken for histologic analysis, then transporting the specimen to a collection device located outside of the endoscope. Biopsies from different lesions or locations can be segregated in separate sample cups to avoid confusion about their site of origination. Furthermore, the MBD collection container will greatly speed up transfer of specimens from the collection device to formalin cups, while eliminating the risk of impalement by the central spike during the retrieval of samples from the cups of the biopsy forceps. The following specific aims will complete MBD validation in preparation for regulatory submission. SA1. Specific Aim 1: (i) Design and implement a Design Trace Matrix (DTM), Risk Management Plan and associated protocols for manufacturing and testing clinical-grade MBDs. (ii) Construct an adequate number of medical devices using contract manufacturers for supplying components for final assembly and packaging by EAD, including a sterilization safety study SA 2: Conduct a phase I Feasibility Study to support a future pivotal trial. This will consist of a RBDPB cross- over trial, as detailed in the Research Strategy section (n = 150). Successful completion of this SBIR funded development program will support the commercialization of a paradigm-shifting diagnostic device that will dramatically improve the process of endoscopic biopsy, while maximizing patient and ancillary staff safety.